Abstract: Objective To investigate the protection and its probably mechanisms of Lycopene (LP) on the mice with liver injury following trans fatty acid (TFA) damage. Methods Forty KM mice (equivalent males and females) were randomly divided into five groups as follows:normal control group (normal saline), TFA group (50 mg/kg body weight TFA) and groups of TFA with low, middle and high dosages treatment LP protection group (50 mg/kg body weight TFA+5, 10, 20 mg/kg body weight LP), with 8 mice in each group (equivalent males and females). All the experimental procedures were intragastrically applied once every other day, eight weeks in total. The tissues were processed as follows:detection serum ALT, AST, TP, ALB, TG, TC, HDL-C, LDL-C content and liver tissue SOD, GSH-Px activity and MDA content. Results In the groups with TFA, the weight increasing of mice and the organ coefficient of liver, ALT, AST, TP, ALB, TG, TC, LDL-C and MDA content were higher than that in the control group (P<0.05) and TP, ALB, HDL-C content were lower (P<0.05). In the groups with TFA, the activity of liver SOD and GSH-Px was decreased (P<0.05). The livers in the TFA group were damaged to different extents. Compared with the groups with TFA, groups of TFA with low, middle and high dosages plus LP, the weight increasing of mice and the organ coefficient of liver, ALT, AST, TP, ALB, TG, TC, LDL-C and MDA content were lower (P<0.05), and TP, ALB, HDL-C content were higher (P<0.05), the activity of liver SOD and GSH-Px was higher (P<0.05). Following LP treatments, the liver damages in the LP groups with different doses were alleviated. Conclusion LP performs the repairing role for the liver via inhibiting the oxidative stress damages caused by TFA, which mechanisms might be correlated to the effects of anti-lipid peroxidation and oxygen free-radical clearing activity.